Automated point-of-care devices for complex sample processing and methods of use thereof
Inventors
Pais, Andrea Maria Dominic • Pais, Rohan Joseph Alexander
Assignees
Publication Number
US-11364495-B2
Publication Date
2022-06-21
Expiration Date
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Abstract
The present invention provides methods and devices for simple, low power, automated processing of biological samples through multiple sample preparation and assay steps. The methods and devices described facilitate the point-of-care implementation of complex diagnostic assays in equipment-free, non-laboratory settings. The invention includes a microfluidic device comprising a reagent-dispensing unit, a sample extraction device and a specimen processing unit.
Core Innovation
The present invention provides methods and devices for simple, low power, automated processing of biological samples through multiple sample preparation and assay steps. The invention includes a microfluidic device comprising a reagent-dispensing unit, a sample extraction device and a specimen processing unit and facilitates the point-of-care implementation of complex diagnostic assays in equipment-free, non-laboratory settings.
The disclosure describes a reagent-dispensing unit (RDU) that overcomes issues related to dead volume retained in microfluidic conduits and stored reagent pouches by packaging an aqueous reagent together with a non-aqueous immiscible reagent in a single reagent pouch sealed by a frangible seal, and by using plungers and a sharp object or protrusion to rupture the sealing layer to deliver reagents into fluidic wells; the immiscible reagent pushes out retained aqueous reagent, collects excess in a waste well, and forms an immiscible barrier that prevents evaporation during heating steps.
The patent further discloses sample extraction devices and specimen processing units that enable sequential reagent delivery, magnetic bead based sample preparation with capture, re-suspend and transport of beads between reagent wells using spatially oriented magnets, integrated heater elements for amplification, and downstream detection such as lateral flow strips on a rotating microfluidic cartridge; [procedural detail omitted for safety].
Claims Coverage
One independent claim is identified. The main inventive features of the independent claim relate to a reagent-dispensing unit integrated with a microfluidic device and specific pouch and actuation elements.
Reagent-dispensing unit with pouch seals
A reagent-dispensing unit comprising a plurality of reagent pouches each comprising one or more reagents and a sealing layer.
Fluidic well with inlet interface
At least one fluidic well comprising an inlet conduit and an interface between the sealing layer and the inlet conduit.
Actuation mechanism to rupture seal
At least one plunger and at least one sharp object or protrusion configured to rupture the sealing layer and deliver the one or more reagents into the microfluidic device when an actuation force is applied to a reagent pouch.
Combined aqueous and immiscible reagent pouch
At least one pouch comprises at least two reagents comprising an aqueous reagent and a non-aqueous immiscible reagent packaged together in a single reagent pouch.
The independent claim principally covers a microfluidic reagent-dispensing unit integrating frangible-sealed reagent pouches, an inlet-interface to fluidic wells, an actuation mechanism (plunger and sharp element) to rupture seals for reagent delivery, and at least one pouch combining aqueous and non-aqueous immiscible reagents.
Stated Advantages
Efficiently delivers all aqueous reagents required for accurately performing a microfluidic cartridge based assay, eliminating the need for sophisticated metering systems for metering precise volumes of aqueous reagent.
Eliminates dead volume issues by using a non-reactive immiscible non-aqueous fluid to push out aqueous reagent and occupy dead spaces in conduits and pouches.
Does not require complex valves or pumps, thereby greatly reducing system complexity.
Volume of the immiscible reagent dispensed is not critical and does not require precise delivery, reducing the need for precise actuation control to ensure run-to-run repeatability.
The immiscible non-aqueous fluid forms a barrier on top of the aqueous fluid to prevent evaporation of the aqueous reagent during heating steps such as thermocycling or heat incubation.
A locking mechanism can lock the plunger in its depressed position to prevent backflow of reagents into the reagent pouch.
Self-contained systems are advantageous for point-of-care settings because they do not require complex, user-driven pipetting or injection steps, reducing hands-on time and user error.
Enables low-power, stand-alone, inexpensive, and disposable instrumentation that can be directly integrated onto the microfluidic device to run automated sample-to-answer sequences.
Documented Applications
Point-of-care implementation of complex diagnostic assays in equipment-free, non-laboratory settings.
A sample-to-answer microfluidic device and assay automation instrument for performing automated assays such as a nucleic acid amplification test (NAAT) on the microfluidic device.
Maximizing sample elution efficiency when transferring a sample from a sample collection device (e.g., a swab) into a medium or buffer on a fluidic device and integrating the sample into the medium or buffer on the fluidic device.
Magnetic bead based sample preparation within a rotating microfluidic cartridge to perform bind, wash, and elute sequences for nucleic acid purification.
Colorimetric detection of amplified products on an integrated lateral flow strip, with amplified product delivery by rupture of a frangible seal.
Sample extraction and processing of swab samples using a sample collection container with a scrubbing insert and a detachable sample processing unit to recover and process swab eluent.
Processing of a variety of biological sample types including saliva, blood, plasma, serum, urine, sputum, CSF, tissue, feces, plant, food, soil, and small organisms as explicitly described in the specification.
Storage of reagents on a microfluidic cartridge in liquid and dried (lyophilized) formats for sequential dispensing and on-chip hydration for assays.
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